Exemplary embodiments of the present invention relate to predicting and classifying the risk of sudden cardiac death for medical patients as well as individuals not exhibiting any health conditions. More specifically, exemplary embodiments relate to detection and analysis of cardiac action potential repolarization phase instability as an indicator for predicting risk of sudden cardiac death for subjects through analysis and classification of cardiac repolarization curves extracted from surface electrocardiogram data recorded for the subjects.
Sudden Cardiac Death (SCD) refers to a natural, rapid, and unexpected death from cardiac causes and is the most common lethal manifestation of heart disease. SCD, which is signaled by abrupt loss of consciousness within one hour of the onset of acute symptoms, claims around 17 million lives every year worldwide and between 500 and 1000 lives per day in the US alone. This constitutes approximately 30 percent of the entire global mortality per annum. Despite major advances in the prevention and treatment of cardiac disease, around 60 percent of cardiac deaths are sudden in nature, and the survival rate from SCD currently stands at 1 percent globally and at 5 percent in the US (see Mehra, R., Global Public Health Problem of Sudden Cardiac Death, Journal of Electrocardiology, November-December 2007, 40, (Suppl. 6) S118-22; Sovari, A. A., Sudden Cardiac Death, retrieved from emedicine.medscape.com, 2009).
The majority of cases of SCD are due to occurrences of ventricular tachycardia (VT) and ventricular fibrillation (VF). VT and VF are responsible for around 6 million deaths per year around the world (see Mehra, R., Global Public Health Problem of Sudden Cardiac Death, Journal of Electrocardiology, November-December 2007, 40, (Suppl. 6) S118-22; Zipes, D. P. Epidemiology and mechanisms of sudden Cardiac Death, Can. J. Cardiol, 2005, 21(A): 37A-40A; Wei Hua, et. al., Incidence of Sudden Cardiac Death in China, JACC, 2009, 54, 1110-8). The most efficient method currently in use for preventing deaths resulting from VF and VT is by using an implanted cardioverter-defibrillator device (ICD), which is a small battery-powered electrical impulse generating device that is implanted in patients who are at risk of sudden cardiac death due to VT and VF. An ICD operates to detect cardiac arrhythmia and correct it by delivering a brief electrical impulse or shock to the heart.
Nevertheless, accurately and dependably predicting risk of SCD due to VT and VF has been difficult to achieve. Methods for detection of VT and VF should be easy to perform, easily available, non-invasive, highly accurate, and cost-effective (see Engel, G., Electrocardiographic Arrhythmia Risk Testing, Current Problems in Cardiology, 2004; 29:357-432; Exner, D. V. et al, Non-invasive risk assessment early after a myocardial infarction, JACC, 2007, 50:2275-84). Current methods for such detection, however, fall short of these standards. For example, applications involving invasive electrophysiological study (EPS) that have been practiced have now become outdated as a predictive procedure for SCD, and current criteria for ICD implantation such as ejection fraction (EF) of less than 30 percent, the New York Heart Association (NYHA) functional classes III and IV, and QRS duration of more than 120 milliseconds are likewise viewed as being far from ideal (see Sovari; Jouven, X., et al., Predicting Sudden Death in the Population, Circulation, 1999, 99:1978-1983; Goldberger, J. J. et al, American Heart Association: Scientific Statement on Noninvasive risk Stratification techniques for Identifying Patients at Risk for Sudden Cardiac Death, JACC, 2008, 52, 1179-99; Riley, L., Risk Stratification for Sudden Death, Today in Cardiology, 2007, 10:24; Noseworthy, P. A., Newton-Cheh, C., Contemporary reviews in Cardiovascular Medicine—Genetic Determinations of Sudden Cardiac Death, Circulation, 2008, 118: 1854-1863; Schwacke, H. et al, Is there any clinical importance of a non-diagnostic baroreflex sensitivity measurement, JACC, 1999, 31(suppl): 1086; Mullner, M. et al, Creatine kinase-mb fraction and cardiac troponin T to diagnose acute myocardial infarction after cardiopulmonary resuscitation, JACC, 1996, 28:1220-1225).